The overall objective of this project is to evaluate the intracellular mechanisms which alter the skeletal muscle function during the known progression of muscle dystrophies in genetically inbred cardiomyopathic Syrian hamsters and in humans with Duchhene muscular dystrophy. This strain of hamsters provides a reliably reproducible model of muscular dystrophy and congestive heart failure, and allows systematic studies of the myopathic processes. Human biopsy studies would allow direct application of this knowledge to the disease. These studies will be made with simplified skinned fiber preparations of muscles to rule out the complicating effects of heterogeneity and extracellular connective tissue. Such preparations will be obtained from psoas (fast muscle) and soleus (slow muscle) fibers in hamsters and from biopsies of quadriceps and gastrocnemius muscles and Duchhene patients. One specific objective is to measure the contraction properties of preparations of randomly selected fibers from each of the muscles, to determine a range of contraction properties within a given muscle and effect of the disease on this distribution. The physiological studies will be correlated with a morphological and histochemical changes in the sampled muscle as well as in the fiber studied. Therefore, the study will help with better characterizing the muscle disease and provide critical tests of the various hypotheses for pathogenesis of myopathy. The Ca and Sr sensitivity of force development and of intrinsic shortening speed will be measured to evaluate the changes in the regulation mechanism in the disease at several selected stages of development. Similarly, the sensitivity of these parameters to ionic strength will be determined to evaluate changes in properties of the specific rate constants of the cross-bridge turnover mechanism. Such studies will be made of the contraction transients as well and will be carried out for 30 days, 75 days, 150 days and 300 days hamsters. Another long term objective of the project is to evaluate the effects of therapeutic drugs (verapamil, isoproteronal and prazosin) on the various contraction derived from these studies of this project will help in the understanding as well as the cure of muscular dystrophy and also possibly of the myocardial failure in congestive disease.